scholarly journals Invertible promoters mediate bacterial phase variation, antibiotic resistance, and host adaptation in the gut

Science ◽  
2019 ◽  
Vol 363 (6423) ◽  
pp. 181-187 ◽  
Author(s):  
Xiaofang Jiang ◽  
A. Brantley Hall ◽  
Timothy D. Arthur ◽  
Damian R. Plichta ◽  
Christian T. Covington ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Phase Variation ◽  
Antibiotic Resistance Genes ◽  
Fecal Microbiota ◽  
Metagenomic Data ◽  
Fecal Microbiota Transplant ◽  
Dna Inversion ◽  
Gut Colonization ◽  
Selective Forces

Phase variation, the reversible alternation between genetic states, enables infection by pathogens and colonization by commensals. However, the diversity of phase variation remains underexplored. We developed the PhaseFinder algorithm to quantify DNA inversion–mediated phase variation. A systematic search of 54,875 bacterial genomes identified 4686 intergenic invertible DNA regions (invertons), revealing an enrichment in host-associated bacteria. Invertons containing promoters often regulate extracellular products, underscoring the importance of surface diversity for gut colonization. We found invertons containing promoters regulating antibiotic resistance genes that shift to the ON orientation after antibiotic treatment in human metagenomic data and in vitro, thereby mitigating the cost of antibiotic resistance. We observed that the orientations of some invertons diverge after fecal microbiota transplant, potentially as a result of individual-specific selective forces.

scholarly journals Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials

2020 ◽  
Author(s):  
Jasmohan S. Bajaj ◽  
Amirhossein Shamsaddini ◽  
Andrew Fagan ◽  
Richard K. Sterling ◽  
Edith Gavis ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Fecal Microbiota ◽  
Fecal Microbiota Transplant

Gut resistome presents a unique biome signature in chronic multi-symptom illness patients and links persistent pro-inflammatory phenotype in a mouse model reversible by fecal microbiota transfer

2021 ◽  
Author(s):  
Dipro Bose ◽  
Somdatta Chatterjee ◽  
Ethan Older ◽  
Ratanesh Seth ◽  
Patricia Janulewicz Lloyd ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Mouse Model ◽  
Resistance Genes ◽  
Intestinal Inflammation ◽  
Antibiotic Resistance Genes ◽  
Chronic Fatigue ◽  
Fecal Microbiota ◽  
Mouse Serum ◽  
War Veterans ◽  
Fecal Microbiota Transplant

Abstract Chronic multi-symptom illness (CMI) affects a subsection of elderly and war veterans and is associated with systemic inflammation, chronic fatigue, pain and neuroinflammation. We showed previously that an altered gut microbiome-inflammation axis aids to the symptom reporting and persistence. Here, a mouse model of CMI and a group of Gulf War veterans’ with CMI showed the presence of an altered host resistome, a signature of antibiotic resistance genes within the microbiome. Results showed that antibiotic resistance genes were significantly altered in the CMI group in both mice and GW veterans when compared to the control. Fecal samples from GW veterans with persistent CMI showed a significant increase of resistance to a wide class of antibiotics and exhibited an array of mobile genetic elements distinct than normal healthy controls. Strikingly, the altered resistome and gene signature were correlated with mouse serum IL6 levels. Altered resistome in mice also correlated strongly with intestinal inflammation, decreased synaptic plasticity that was reversible with fecal microbiota transplant (FMT), a tool to restore a healthy biome. The results indicate an emerging linkage of the gut resistome and CMI and might be significant in understanding the risks to treating hospital acquired infections in this population.

scholarly journals PRO: Carbapenems should be used for ALL infections caused by ceftriaxone-resistant Enterobacterales

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
David L Paterson ◽  
Burcu Isler ◽  
Patrick N A Harris
Keyword(s):  
Antibiotic Resistance ◽  
Observational Studies ◽  
Randomized Trials ◽  
Antibiotic Resistance Genes ◽  
Definitive Treatment ◽  
In Vitro Activity ◽  
Genes Encoding ◽  
Amoxicillin Clavulanate ◽  
Trial Outcomes

Abstract Ceftriaxone resistance in the Enterobacterales is typically the result of production of ESBLs or AmpC β-lactamases. The genes encoding these enzymes are often co-located with other antibiotic resistance genes leading to resistance to aminoglycosides, quinolones and trimethoprim/sulfamethoxazole. Carbapenems are stable to ESBLs and AmpC giving them reliable in vitro activity against producers of these β-lactamases. In contrast, piperacillin/tazobactam and amoxicillin/clavulanate are compromised by co-production of OXA-1, which is not inhibited by tazobactam or clavulanate. These in vitro findings provide an explanation for the MERINO trial outcomes, where 3.7% (7/191) randomized to meropenem died compared with 12.3% (23/187) randomized to piperacillin/tazobactam as definitive treatment of bloodstream infection due to ceftriaxone-resistant organisms. No randomized trials have yet put cefepime and carbapenems head to head, but some observational studies have shown worse outcomes with cefepime. We argue that carbapenems are the antibiotics of choice for ceftriaxone-resistant Enterobacterales.

scholarly journals Diagnostic Microbiology: Present Status and Future Prospect

2017 ◽  
Vol 2 (2) ◽  
pp. 42-47
Author(s):  
Shahanara Begum ◽  
Md. Abdullah Yusuf ◽  
Bhuiyan Mohammad Mahtab Uddin
Keyword(s):  
Infectious Disease ◽  
Mass Spectrometry ◽  
Antibiotic Resistance ◽  
Historical Perspective ◽  
Future Prospect ◽  
Antibiotic Resistance Genes ◽  
Require Time ◽  
Prior Use ◽  
Diagnostic Microbiology

Diagnostic Microbiology is the tool that makes it possible to identify the exact pathogens of infectious diseases and the most optimal therapy at the level of individual patients. Conventional methods require time to grow the microbes in vitro under specific conditions and not all microbes can easily be cultured. This is followed by biochemical methods for identification which further makes the process lengthy. Transport of the specimens under less than ideal conditions, prior use of antibiotics and small number of organisms are among the factors that render culture-based methods less reliable. Newer methods depend on amplification of nucleic acids followed by use of probes for identification. This mitigates the need for higher microbial load, presence of metabolically active viable organisms and shortens the time. These methods can be used to detect antibiotic resistance genes directly from the specimen and help direct targeted therapy with efficacy. Since these methods will not fulfill all the diagnostic needs, a second approach is being used to shorten the time to identification after the organism has already grown. Mass spectrometry and bioinformatics are the tools making this possible. This review gives a historical perspective on diagnostic microbiology, discusses the pitfalls of current methodology and provides an overview of newer and future methods.Bangladesh Journal of Infectious Disease 2015;2(2):42-47

scholarly journals Removal of Antibiotic Resistance Gene-Carrying Plasmids from Lactobacillus reuteri ATCC 55730 and Characterization of the Resulting Daughter Strain, L. reuteri DSM 17938

2008 ◽  
Vol 74 (19) ◽  
pp. 6032-6040 ◽  
Author(s):  
Anna Rosander ◽  
Eamonn Connolly ◽  
Stefan Roos
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Lactobacillus Reuteri ◽  
Antibiotic Resistance Gene ◽  
Genetically Modify ◽  
Antibiotic Resistance Genes ◽  
Probiotic Strain ◽  
Probiotic Properties ◽  
Food Borne

ABSTRACT The spread of antibiotic resistance in pathogens is primarily a consequence of the indiscriminate use of antibiotics, but there is concern that food-borne lactic acid bacteria may act as reservoirs of antibiotic resistance genes when distributed in large doses to the gastrointestinal tract. Lactobacillus reuteri ATCC 55730 is a commercially available probiotic strain which has been found to harbor potentially transferable resistance genes. The aims of this study were to define the location and nature of β-lactam, tetracycline, and lincosamide resistance determinants and, if they were found to be acquired, attempt to remove them from the strain by methods that do not genetically modify the organism before subsequently testing whether the probiotic characteristics were retained. No known β-lactam resistance genes was found, but penicillin-binding proteins from ATCC 55730, two additional resistant strains, and three sensitive strains of L. reuteri were sequenced and comparatively analyzed. The β-lactam resistance in ATCC 55730 is probably caused by a number of alterations in the corresponding genes and can be regarded as not transferable. The strain was found to harbor two plasmids carrying tet(W) tetracycline and lnu(A) lincosamide resistance genes, respectively. A new daughter strain, L. reuteri DSM 17938, was derived from ATCC 55730 by removal of the two plasmids, and it was shown to have lost the resistances associated with them. Direct comparison of the parent and daughter strains for a series of in vitro properties and in a human clinical trial confirmed the retained probiotic properties of the daughter strain.

scholarly journals Characterization of antibiotic resistance genes in the species of the rumen microbiota

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yasmin Neves Vieira Sabino ◽  
Mateus Ferreira Santana ◽  
Linda Boniface Oyama ◽  
Fernanda Godoy Santos ◽  
Ana Júlia Silva Moreira ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Animal Health ◽  
Antibiotic Resistance Genes ◽  
Tetracycline Resistance ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Ruminal Bacteria ◽  
Genes Encoding

AbstractInfections caused by multidrug resistant bacteria represent a therapeutic challenge both in clinical settings and in livestock production, but the prevalence of antibiotic resistance genes among the species of bacteria that colonize the gastrointestinal tract of ruminants is not well characterized. Here, we investigate the resistome of 435 ruminal microbial genomes in silico and confirm representative phenotypes in vitro. We find a high abundance of genes encoding tetracycline resistance and evidence that the tet(W) gene is under positive selective pressure. Our findings reveal that tet(W) is located in a novel integrative and conjugative element in several ruminal bacterial genomes. Analyses of rumen microbial metatranscriptomes confirm the expression of the most abundant antibiotic resistance genes. Our data provide insight into antibiotic resistange gene profiles of the main species of ruminal bacteria and reveal the potential role of mobile genetic elements in shaping the resistome of the rumen microbiome, with implications for human and animal health.

scholarly journals Intra- and Interspecies Conjugal Transfer of Tn916-Like Elements from Lactococcus lactis In Vitro and In Vivo

2009 ◽  
Vol 75 (19) ◽  
pp. 6352-6360 ◽  
Author(s):  
Joanna Boguslawska ◽  
Joanna Zycka-Krzesinska ◽  
Andrea Wilcks ◽  
Jacek Bardowski
Keyword(s):  
Antibiotic Resistance ◽  
Lactococcus Lactis ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Tetracycline Resistance ◽  
Raw Milk ◽  
M Gene ◽  
Transfer Resistance

ABSTRACT Tetracycline-resistant Lactococcus lactis strains originally isolated from Polish raw milk were analyzed for the ability to transfer their antibiotic resistance genes in vitro, using filter mating experiments, and in vivo, using germfree rats. Four of six analyzed L. lactis isolates were able to transfer tetracycline resistance determinants in vitro to L. lactis Bu2-60, at frequencies ranging from 10−5 to 10−7 transconjugants per recipient. Three of these four strains could also transfer resistance in vitro to Enterococcus faecalis JH2-2, whereas no transfer to Bacillus subtilis YBE01, Pseudomonas putida KT2442, Agrobacterium tumefaciens UBAPF2, or Escherichia coli JE2571 was observed. Rats were initially inoculated with the recipient E. faecalis strain JH2-2, and after a week, the L. lactis IBB477 and IBB487 donor strains were introduced. The first transconjugants were detected in fecal samples 3 days after introduction of the donors. A subtherapeutic concentration of tetracycline did not have any significant effect on the number of transconjugants, but transconjugants were observed earlier in animals dosed with this antibiotic. Molecular analysis of in vivo transconjugants containing the tet(M) gene showed that this gene was identical to tet(M) localized on the conjugative transposon Tn916. Primer-specific PCR confirmed that the Tn916 transposon was complete in all analyzed transconjugants and donors. This is the first study showing in vivo transfer of a Tn916-like antibiotic resistance transposon from L. lactis to E. faecalis. These data suggest that in certain cases food lactococci might be involved in the spread of antibiotic resistance genes to other lactic acid bacteria.

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